Control of ventilation is very dependent upon acid-base conditions in the central nervous system (CNS). Associated with these acid-base conditions are metabolic factors, whose relationship to CNS hydrogen ion homeostasis is not well understood. Specific endogenously synthesized CNS amino acids may have important effects on respiration. Our principal hypothesis is that brain bicarbonate, ammonia, and certain endogenously generated amino acids (specifically the putative neurotransmitters gamma amino butyric acid (GABA) and glutamic acid) participate significantly in the central chemical control of respiration, and that this control is effected by exchange of specific metabolic precursors between different metabolic pools in the CNS. Glutamine is such a precursor. Systemically administered ammonia and bicarbonate tracers labeled respectively with isotopic nitrogen and carbon are both rapidly and preferentially incorporated into brain glutamine. Based upon evidence of at least two intracellular metabolic pools or compartments of GABA and glutamic acid in the brain and that glutamic acid and GABA have opposing effects on respiratory neurons, we hypothesize that glutamine participates isgnificantly in CNS chemical control of respiration by acting as a key intermediate metabolic agent which moves from glial cells where it is synthesized, to neurons where it serves as a precursor for synthesis of GABA. Glutamine synthesis directly relates to CNS ammonia metabolism, and glutamine concentration increases parallel to that of bicarbonate. We propose to study this potentially important metabolic mechanism in an intact animal preparation (dogs), using a tracer method to label the precursors in the CNS. The isotope substances will be 13N-ammonia and 11C-bicarbonate introduced intravascularly and intraventricularly to study the interdependence of principal radiotracer-labeled metabolic products of ammonia and of bicarbonate in blood and CSF. The relationship between H+ homeostasis and amino acid metabolism would contribute to our understanding of respiratory drive and CNS metabolic functions.